Automated red blood cell exchange for acute drug removal in a patient with sirolimus toxicity

Abstract

Sirolimus is an immunosuppressant used to prevent graft versus host disease in allogeneic hematopoietic stem cell transplant recipients. It has a large volume of distribution (12 ± 7.5 l/kg) and within the intravascular space ∼95% of it is bound to red blood cells. Because of potential toxic effects at high trough levels, therapeutic drug monitoring is recommended for sirolimus. We present a case of severe hepatic dysfunction due to Hepatitis B and sirolimus toxicity, in a 51-year-old male stem cell transplant recipient. An automated red cell exchange decreased his blood sirolimus level from 22.6 to 10.3 ng/ml (55% reduction) and improved his liver enzymes. Re-equilibration of sirolimus from other compartments to the blood necessitated a series of four red cell exchanges, after which the sirolimus level was 4.7 ng/ml. Although the patient ultimately succumbed to multiorgan failure, red cell exchange may be considered for acute removal of sirolimus in selected patients.

Successful management of sirolimus toxicity in a hematopoietic stem cell transplant patient using automated red blood cell exchange

“…The sequestration of sirolimus, like tacrolimus, into blood cells is believed to be mainly due to the presence of binding proteins such as FK binding protein 7 . Galera et al 14 recently tested the hypothesis that sirolimus, which is heavily bound to RBCs, could be removed from the blood by removing erythrocytes via automated RBC exchange. Although they were able to lower the blood sirolimus concentration to therapeutic levels, their patient died from multiorgan failure.…”

“…Based on a recent suggestion that RBC apheresis could lower the blood sirolimus levels, we effectively treated with RBC exchange. 14…”

“…We present a case of a 19‐year‐old female with sickle cell disease, hemoglobin SS, presenting with sirolimus toxicity after recently undergoing hematopoietic stem cell transplantation. Based on a recent suggestion that RBC apheresis could lower the blood sirolimus levels, we effectively treated with RBC exchange 14 …”

Vascular access for red blood cell exchange

“…RBC exchange reportedly has been used in other clinical scenarios in which RBCs are determined to be the primary cause of clinical symptoms, and replacement could change the disease course. Examples include toxicity due to tacrolimus and sirolimus; drugs that are highly bound to RBCs, as well as carbon monoxide poisoning and severe acquired methemoglobinemia . Mitigation of delayed hemolytic transfusion reactions has also been described, in which RBC exchange was used to remove potential RBC targets of hemolysis with clinical improvement .…”

“…Examples include toxicity due to tacrolimus and sirolimus; drugs that are highly bound to RBCs, as well as carbon monoxide poisoning and severe acquired methemoglobinemia. [23][24][25][26][27] Mitigation of delayed hemolytic transfusion reactions has also been described, in which RBC exchange was used to remove potential RBC targets of hemolysis with clinical improvement. 28,29 These reports are examples of the potentially expanding role for RBC exchange in medicine, although more data are required before such indications merit official recommendations.…”